In this project, we will evaluate 8 novel 99mTc(III) complexes [99mTc(S-R)(CDO)(CDOH)2B-Me] (R = P1 - P24) as SPECT radiotracers myocardial perfusion imaging. Sprague-Dawley (SD) rats will be used to evaluate their heart uptake and biodistribution. These studies are designed to answer the following three fundamental questions: (1) Are they able to localize and retain in heart (high heart uptake and long myocardial retention)? (2) What is the impact of PEG groups on heart uptake and liver clearance of 99mTc radiotracers? (3) Which is the best radiotracer with respect to the heart uptake, myocardial retention and heart/liver ratios? The main objective of this project is to increase the myocardial retention and minimize liver uptake of novel 99mTc(III) radiotracers while maintaining their high heart uptake. Hypothesis and Strategy: We hypothesize that thiolates are able to increase the myocardial retention of their 99mTc(III) complexes [99mTc(S-R)(CDO)(CDOH)2BMe] (R = P1 - P24) by preventing their hydrolysis in vivo because thiolate-S forms a stronger bond with Tc(III) than Cl. We also hypothesize that polyether groups will increase the myocardial retention and liver clearance of 99mTc(III) complexes since it has been well-established that PEG groups can increase the blood retention times of therapeutics, and our studies clearly showed that polyether groups are able to improve liver clearance of cationic 99mTc radiotracers. To test these hypotheses, we developed a two-step strategy. In first step, we will prepare complexes [99mTc(S-R)(CDO)(CDOH)2B-Me] (R = P1 - P24). Different R groups are used to balance their lipophilicity so that their heart uptake and T/B ratios can be optimized in a systematic fashion. In the second step, we will evaluate their heart uptake and biodistribution in SD rats. 99mTc-Teboroxime will be always used as the control for comparison purposes. The results from these studies will allow us to select an optimal candidate for further evaluations in the future. Clinical Significance. More than 70 million Americans currently live with cardiovascular diseases, which lead to >910,000 deaths each year. Rapid and accurate diagnosis in CAD patients is highly desirable so that appropriate therapeutic regimens can be given. Funding and successful completion of this project may lead to new 99mTc radiotracers that have very high first-pass extraction fraction with the heart/liver ratios much better than tha of 99mTc-Teboroxime. High heart uptake with better heart/liver ratios will allow for early acquisition of images, and improve the image quality by reducing scatter from liver radioactivity. High first-pass extraction and linear relationship between the blood flow rate and the radiotracer myocardial uptake will permit better detection of the presence and extent of coronary disease, and more precise delineation of myocardial perfusion defects, which is of considerable benefit in management of patients with known or suspected CAD and assessing risk of future cardiac events, particularly myocardial infarction and death.